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Key Questions:
- What is the optimal
focus for future clinical trials?
- What are the most
promising scientific leads that will result in the next generation of
clinical trials?
Outcomes and Discussion
Points:
- Current knowledge
of pathogenesis (Drs. Fearon & Hamilton)
- Major mutated
pathways
- Familial cancers
can demonstrate mutated or wild-type genotype
- Prognostic markers
- Specific markers
(Drs. Hamilton & Warren)
- Validation
and pathologic correlates (Dr. Compton)
- Rigidity of
current staging system (Dr. Compton)
- Study problems:
low tissue resources and statistical pitfalls (Drs. Compton &
Sargent)
- Therapy
- Present status
(Dr. O'Connell)
- Anti-angiogenic
targets (Dr. Ellis)
- Immunotherapy
(Dr. Foon)
- Signaling targets
(Dr. Adjei)
- Clinical trial
design models for examining new cytostatic compounds
- Endpoint issues
(phases I-II) (Dr. Eisenhauer)
- Statistical
issues (phases I-III) (Dr. Korn)
- New imaging technology
- Virtual colonoscopy,
CT, MRI (Dr. Ros)
- PET (Dr. Graham)
- Percutaneous
ablation (Dr. van Sonnenberg)
- Surgical management
- Trials: not
enough adjuvant therapy and too much surgical nuance (Dr. Wolmark)
- Various surgical
procedures (Dr. Petrelli), including sentinel lymph nodes (Dr. Kemeny)
- Treatment tailoring
via predictive markers
- Levamisole
trials (Dr. Benson)
- 5-FU and cisplatin
trials (Drs. Saltz & Danenberg)
- Radiation
(p21 WAF1) (Dr. Hamilton)
- Treatment failure
- Drug penetration
(Dr. Tannock)
- Tumor repopulation
(Dr. Tannock)
- Radiosensitizing
(mainly via ras pathway inhibition) (Dr. McKenna)
- Chemosensitizing
(Dr. Allegra)
- Barriers to clinical
trials (Dr. Mayer, summary)
Key Recommendations:
- Develop traditional
and translational advances in concert in order to correlate molecular
markers with more established pathological/clinical characteristics.
- Develop a more
"plastic" staging system able to incorporate molecular markers
once they become validated.
- Validate prognostic
and predictive tissue-based markers for improved staging and agent screening.
- Place less emphasis
on tumor regression rate and more on progression rate in phase II studies
of cytostatic agents.
- Establish a national
tumor bank with a searchable database and potential mandatory submission.
- Combine tissues
from different protocols to perform same/overlapping analysis on them
(i.e., do not tie a specimen to one protocol only).
- Examine application
of individualized, risk-adapted therapy, in which treatment choice is
optimized based on tumor biological profiling. Trials must attempt to
show benefit of pre-selecting patients for therapy based on markers.
- Study new agents
in combination during phase I trials if they are to be used in combination
in a clinical setting.
- Define the role
of new, costly imaging and ablation techniques.
- Work to modify
emerging, multiple mechanisms of treatment resistance.
- Continue refining
procedures in prevention, including chemoprevention via Cox inhibitors
and screening using virtual colonography.
- Move predictive
markers into the adjuvant setting. This transition will require assessing
their applicability to metastatic disease.
- Enhance surgeon
willingness to study adjuvant therapy in surgical trials.
- Facilitate participation
of physicians on trials (e.g., training) to close gap between participation
rates and surge of new agents in development.
- Improve prognostic/predictive
factor studies by:
- Using tissue
series specific to well-defined patient populations with established
baseline characteristics (not convenience samples)
- Standardizing
assay techniques, interpretation, and reporting
- Validating
DNA micro-array technology
- Addressing
missing data due to technology or series constraints
- Performing
more multivariate analyses
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